Method for heart transplant monitoring and analog telemetry calibration

ABSTRACT

A cardiac pacemaker with an analog telemetry system. A calibration circuit within the pacemaker is adapted to provide a reference signal of known character to the pacemaker&#39;s telemetry system. The reference signal is transmitted across the telemetry link as if it were an actual cardiac signal, and received by an external programmer. Since the reference signal has known, predetermined qualities, the programmer can automatically calibrate and scale the telemetry signal from the pacemaker, thereby increasing the accuracy of the telemetry channel. The increased accuracy is particular useful in assessing rejection of a transplanted heart, which is known to be associated with a 15% decline in the peak R-wave amplitude of the cardiac signal.

This application is a continuation in part of application Ser. No.08/250,408, filed May 27, 1994, now abandoned, which is a division ofapplication Ser. No. 07/907,259, filed Jul. 1, 1992, now U.S. Pat. No.5,402,794.

FIELD OF THE INVENTION

This invention relates to the field of cardiac pacemakers, and moreparticularly to a pacemaker having an automatic calibration signal foran analog telemetry channel.

BACKGROUND OF THE INVENTION

As of Jan. 1, 1991, over 16,000 heart transplants have taken placeworldwide, more than 87% of these since 1984 (according to Kreitt etal., "The Registry of the International Society for Heart and LungTransplantation: Eight Annual Report", The Journal of Heart and LungTransplantation, Number 4, July-August 1991, pp. 491-498). Rejection ofthe transplanted heart within two years is the cause of death in 40% ormore of all cases. Currently, the preferred method for monitoringrejection is by serial transvenous endomyocardial biopsy. Such aprocedure is invasive and relatively traumatic, and must usually beperformed at specialized facilities. Typically, two such tests areperformed during the first six post-implant months; thereafter, thetests are given less frequently, but throughout the patient's lifetime.Up to a day may be required to obtain results from such a test. Oneknown shortcoming of the serial transvenous endomyocardial biopsy inevaluating heart rejection is that existing scar tissue in the heart,which can occur for various reasons other than heart rejection, can beerroneously interpreted as indicating rejection.

It has also been found, however, that certain features of the electricalcardiac signal in transplant patients may also be utilized as anindicator of heart rejection. See, e.g., Warnecke et al., "NoninvasiveMonitoring of Cardiac Allograft Rejection by Intramyocardial ElectrogramRecordings", Circulation 74 (suppl. III), III-72-III-76, 1986. Inparticular, it has been found that the onset of heart rejection isaccompanied by a reduction of up to 15% in the magnitude of intracardiacR-wave and T-wave peaks. See, e.g., Rosenbloom et al., "NoninvasiveDetection of Cardiac Allograft Rejection by Analysis of the UnipolarPeak-to-Peak Amplitude of Intramyocardial Electrograms ", Ann. Thorac.Surg., 1989;47:407-411; see also, e.g., Grace et al., "Diagnosis ofEarly Cardiac Transplant Rejection by Fall in Evoked T Wave AmplitudeMeasured Using an Externalized QT Driven Rate Responsive Pacemaker",PACE, vol. 14, June 1991. The ability to monitor and detect thisphenomenon would therefore facilitate the early detection and treatmentof rejection. To this end, an implantable pacemaker with an accurateanalog telemetry channel for transmitting intracardiac signals wouldgreatly enhance the ability of a monitoring physician to assess thecardiac condition.

Intracardiac electrogram signals have been used to evaluate heartrejection. Typically, however, several or perhaps up to five or moreepicardial leads may be used for this purpose, since it is believed thatthe manifestations of heart rejection are initially localized and canbegin at various sites in the heart muscle.

The intracardiac leads associated with an implanted pacemaker might alsobe used in the evaluation of cardiac signals. Unfortunately, eventoday's state-of-the-art pacemakers have rather inaccurate telemetrychannels, varying greatly in their response from one device to anotherand susceptible to problems with drift, change with temperature, andbattery condition. The inaccuracies in the peripheral (programmer) cancompound the pacemaker and telemetry channel errors. In some cases, theaccuracy of a telemetered intracardiac EGM signal from an implantedpacemaker may be only ±35%.

SUMMARY OF THE INVENTION

It is believed by the inventors, therefore, that it would be desirableto provide a more accurate analog telemetry channel for an implantablecardiac pacemaker, so that an accurate and reliable assessment ofcardiac activity can be made. In accordance with the present invention,a signal is provided to automatically calibrate a pacemaker's analogtelemetry channel. The increased accuracy of the telemetered EGM signalwould allow it to be used not only in transplant rejection monitoring,but also for measuring amplitude and slew rate in cardiac signals,evaluation of lead maturation effects, general pacemaker systemtroubleshooting, and congestive heart failure (CHF) monitoring.

In accordance with one embodiment of the present invention, a known andaccurate test signal at the lead tip electrode is transmitted throughthe telemetry channel, allowing the external programmer or otherperipheral to automatically calibrate and auto-range the entiretelemetry system, which includes the pacemaker filtering circuitry,pacemaker gain control circuitry, a voltage-to-frequency converter orsome other type analog-to-digital converter, a data encoder, radiofrequency link, a data decoder, and signal reconstruction and displaycircuitry.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other aspects of the present invention will be bestunderstood with reference to the following detailed description of aspecific embodiment of the invention, when read in conjunction with theaccompanying drawings, wherein:

FIG. 1 is an illustration of a pacemaker and pacemaker leads inaccordance with one embodiment of the present invention, implanted in apatient;

FIG. 2 is an illustration of the pacemaker and leads from FIG. 1;

FIG. 3 is a block diagram showing a portion of the circuitry of thepacemaker of FIG. 1 and an external programmer;

FIG. 4 is a timing diagram illustrating clock signals utilized by thecircuitry of FIG. 3;

FIG. 5 is a block diagram of the calibration circuit of FIG. 3;

FIG. 6 is a schematic diagram of the calibration circuit of FIG. 3;

FIG. 7 is a timing diagram illustrating signals in the calibrationcircuit of FIG. 6;

FIGS. 8a and 8b are timing diagrams illustrating the calibration signalafter transmission to the programmer of FIG. 3;

FIG. 9 is a functional block diagram of the programmer of FIG. 3; and

FIG. 10 is a block diagram of the circuitry within the programmer ofFIGS. 3 and 9 which calibrates the received analog telemetry from thepacemaker of FIGS. 1-7.

DETAILED DESCRIPTION OF A SPECIFIC EMBODIMENT OF THE INVENTION

In FIG. 1, a pacemaker 10 in accordance with one embodiment of thepresent invention is shown implanted in a patient 12. Pacemaker 10 iselectrically coupled to heart 16 of patient 12 by means of four unipolarepicardial leads 18-1, 18-2, 18-3, and 18-4. One pacemaker which may bereadily adapted for use in accordance with the presently disclosedembodiment of the invention is disclosed in U.S. Pat. No. 5,052,388issued to Sivula et al. on Oct. 1, 1991, which patent is herebyincorporated by reference in its entirety. It is believed by theinventors, however, that from the following detailed description of aspecific embodiment of the present invention it should be apparent to aperson of ordinary skill in the pacemaker art how the present inventionmay be practiced in conjunction with a variety of known pacemakerdesigns.

As shown in FIG. 2, pacemaker 10 is provided with a connector block 11for receiving connector pins 20 and 22 of two "IS-1 to bifurcated"adapters 24 and 26. Adapters 24 and 26 allow the four unipolar leads18-1, 18-2, 18-3, and 18-4 to be interfaced with industry standard IS-1connection points in dual bipolar connector block 11. Leads 18-1, 18-2,18-3, and 18-4 may be Medtronic Models 5069 or 5071 Unipolar Epicardialleads or the like. Adapters 24 and 26 may be, for example, Model5866-24M IS-1 to bifurcated adapters manufactured and commerciallyavailable from Medtronic, Inc., Minneapolis, Minn. In an alternativeembodiment, a connector block 11 capable of receiving all four leads18-1, 18-2, 18-3, and 18-4 could be provided, thereby eliminating theneed for adapters 24 and 26.

Turning now to FIG. 3, a block diagram showing selected relevantportions of internal circuitry of pacemaker 10, as well as an externalprogrammer 32 which communicates with pacemaker 10 via a radio-frequencytelemetry link. In FIG. 3, leads 18-1, 18-2, 18-3, and 18-4 are shownbeing directly connected to a multiplexer 30 in pacemaker 10, it beingunderstood that adapters 24 and 26 may be required to facilitate theconnection of four leads to pacemaker 10, as previously described withreference to FIG. 2.

Multiplexer 30 functions to sequentially couple each of leads 18-1,18-2, 18-3, and 18-4 one at a time to internal conductor 34 of pacemaker10. For example, and as shown in FIG. 3, a four-phase clock comprisingindividual phase signals φ₁, φ₂, φ₃, and φ₄ may be applied tomultiplexer 30, such that lead 18-1 is coupled to conductor 34 duringassertion of φ₁, lead 18-2 is coupled to conductor 34 during assertionof φ₂, and so on. It is believed that the design and implementation ofmultiplexer 30 would be a matter of routine to a person of ordinaryskill in the circuit art. If clock signals φ₁, φ₂, φ₃, and φ₄ shown inFIG. 4 were applied to multiplexer 30, for example, each one of leads18-1, 18-2, 18-3, and 18-4 would be coupled to conductor 34 for1.95-mSec at a time, 128 times per second.

A pacing output circuit 36 is also shown in FIG. 3. The inventors havecontemplated several different pacing arrangements for pacemaker 10. Oneor more of leads 18-1, 18-2, 18-3, and 18-4 could be utilized as both apacing and sensing lead. This can be implemented in two ways: eithermultiplexer 30 may be controlled by signals φ₁, φ₂, φ₃ and φ₄ to applypacing pulses produced on line 40 by pacing output circuit 36 to aselected one or more of leads 18-1, 18-2, 18-3, and 18-4; or pacingoutput circuit could provide pacing pulses on line 40' to a lead selectcircuit 42 adapted to convey pacing pulses on line 40' to a selected oneor more of leads 18-1, 18-2, 18-3 and 18-4, the selection beingindicated, for example, by means of control signals from pacemakercontrol circuitry not shown in FIG. 3.

Cardiac electrical signals from leads 18-1, 18-2, 18-3, and 18-4 areconducted on line 34 to a bandpass filter circuit 44, which in thepresently disclosed embodiment of the invention comprises a high-passfilter made up of a capacitor 46 and a resistor 48, and a low-passfilter made up of resistor 50 and capacitor 52. In the presentlypreferred embodiment of the invention, bandpass filter 44 has ahigh-pass pole at 0.072-Hz and a low-pass pole at 182-Hz.

After filtering, cardiac signals from leads 18-1, 18-2, 18-3 and 18-4are applied to a telemetry circuit 54. A telemetry circuit that issuitable for the purposes of the present invention is described in U.S.Pat. No. 4,556,063 issued to Thompson et al. on Dec. 3, 1985 entitled"Telemetry System for a Medical Device", which patent is herebyincorporated by reference in its entirety. Another telemetry systemsuitable for the purposes of the present invention is disclosed in U.Spatent application Ser. No. 07/765,475 in the name of Wyborny et al.,entitled "Telemetry Format for Implanted Medical Device", which patentis also incorporated herein by reference in its entirety. Telemetrycircuit 54 is coupled to a radio-frequency (RF) transmitting/receivingantenna 56 capable of transmitting signals to a compatible antenna 58associated with external programmer 32. Programmer 32 may also haveassociated therewith various display devices such as a CRT 60 or a paperstrip recorder 62, allowing a physician to view the telemetered EGMsignal.

Further in accordance with the presently disclosed embodiment of theinvention, pacemaker 10 is provided with a calibration circuit 64coupled to conductor 34. As will be hereinafter described in greaterdetail, calibration circuit 64 is adapted to generate on conductor 34known "test" or "reference" signals that may be applied to thepacemaker's telemetry channel. Upon receipt of this reference signal,external programmer 32 is thus able to automatically calibrate andauto-range the complete system, compensating for the effects of filter44, pacemaker circuitry gain variability, telemetry system conversioninaccuracies, RF link decoding variations (i.e., "noise"), andperipheral ranging, signal reconstruction variations and inaccuracies.

According to one embodiment of the present invention, the referencesignal generated by calibration circuit 64 is a 0.5-Hz square wavepassed through a low pass filter at 10-mV amplitude, that is switchedinto the telemetry channel (i.e., onto conductor 34) for processing andtransmission to programmer 32. Programmer 32 then uses the referencesignal to calibrate the telemetry channel and automatically set therange of the received signal for display on CRT 60 or strip recorder 62.Calibration circuit 64 is also capable of producing a "differentialwave" output reference signal, produced by differentiation of the squarewave reference signal at each pulse edge. The "differential wave" signalthus comprises a stream of alternating positive and negative voltagespikes having a peak magnitude of ±10-mV. The maximum value of thedifferential signal, after transmission across the telemetry link, wouldbe detected in programmer 32 using a peak detector for each polarity.The advantage of the "differential wave" reference signal is that itallows accurate, simultaneous dual-polarity calibration of the telemetrychannel.

Referring now to FIG. 5, a block diagram of calibration circuit 64 isshown. It is to be understood in FIG. 5 that the various input signalsto calibration circuit 64 are provided from elsewhere in the circuitryof pacemaker 10. For example, the signals SQ₋₋ WAVESEL and DIF₋₋ CALSELare provided from controller circuitry (not shown) to enable selectionof either a square-wave reference signal or a "differential wave"reference signal.

The VREFIN input signal to calibration circuit 64 is a preciselyregulated 1.200-V reference voltage that is applied to voltage divider66. The 1.200-V reference voltage may be provided, for example, by aconventional band gap voltage reference circuit. Such circuits produce areference voltage which is constant with respect to supply voltage andtypically have temperature coefficients less than 100 ppm.Alternatively, other types of known, high accuracy reference voltagecircuitry may be employed. Voltage divider 66 derives a preciselyregulated 10-mV signal that is applied to a 0.5-Hz oscillator circuit68.

The CLK₋₋ 0₋₋ 5 input signal to oscillator 68 is a 0.5-Hz clock signal.The CALON input signal enables voltage divider 66 and oscillator 68;thus, when CALON is not asserted, voltage divider 66 and oscillator 68are disabled and draw no bias current. This is particularly desirable inimplanted medical devices, where power conservation is critical tomaximum device longevity. Finally, the LP1KHZ₋₋ CLK input signal tocalibration circuit 64 is a 1-kHz clock signal utilized by a 5-Hzlow-pass filter circuit 70.

A schematic diagram of calibration circuit 64 is shown in FIG. 6. Asshown in FIG. 6, a number of internal phase signals P1, NP1, P2, and NP2are derived from the CLK₋₋ 0₋₋ 5 input signal as applied to anon-overlap (NOLS) shifter 74; these phase signals are used elsewhere inthe calibration circuit, as shown in FIG. 6, to enable varioustransmission gates T1, T2, and so on.

With continued reference to FIG. 6, the CALON signal enables amplifierAMP1 prior to a calibration pulse. As would be appreciated by one ofordinary skill in the circuit art, AMP1 is an operationaltransconductance amplifier. The VREFIN voltage is sampled on capacitorC1 (which in the presently preferred embodiment of the invention has acapacitance of 1.14-pF) during phase 2 (i.e., when P2 is asserted). Alsoduring P2, the offset for amplifier AMP1 is sampled on capacitor C2(with capacitance of 120-pF) to implement a standard offset compensationscheme. During phase 1 (i.e., when P1 is asserted), the sampled voltageis divided by the ratio C1/C2. The DIF₋₋ CALSEL input enables transistorTR3, allowing the calibration pulses output from AMP1 to appear on theDIFF₋₋ WAVE output line.

The SQ₋₋ WAVESEL input, when asserted, enables transistor TR2, gatingthe calibration pulse output from AMP1 through a low-pass switchedcapacitor filter with a 5-Hz pole formed by 1/2πRC where R=1/fC.

A timing diagram illustrating the relationship between the varioussignals in the schematic diagram of FIG. 6 is shown in FIG. 7. As shownin FIG. 7, the SQUARE₋₋ WAVE output signal is a simple 0.5-Hz, 10-mVsquare wave, while the DIFF₋₋ WAVE output signal is a stream ofalternating positive and negative spikes having peak voltages of 10-mV.

A generalized block diagram of programmer 32 in accordance with thepresently disclosed embodiment of the invention is provided in FIG. 9.As shown in FIG. 9, programmer 32 is a personal computer-typemicroprocessor-based device incorporating, a central processing unit150, which may be, for example, an Intel 80386 microprocessor or thelike. A system bus 151 interconnects CPU 150 and various othercomponents of programmer 32. For example, bus 151 provides a connectionbetween CPU 150 and a hard disk drive 152 storing operationalprogramming for programmer 32. Also coupled to system bus 151 is agraphics circuit 153 and an interface controller module 154. Graphicscircuit 153, in turn, is coupled to a graphics display screen 155, whichin the case of the Medtronic Model 9760 programmer is a cathode ray tube(CRT) screen 155 having a resolution of 720×348 pixels. In the presentlypreferred embodiment of the invention, screen 155 is of the well-known"touch sensitive" type, such that a user of programmer 32 may interacttherewith through the use of a stylus 156, also coupled to graphicscircuit 153, which is used to point to various locations on screen 155.Various touch-screen assemblies are known and commercially available.

With continued reference to FIG. 9, programmer 32 further comprises aninterface module 157 which includes digital circuitry 158, non-isolatedanalog circuitry 159, and isolated analog circuitry 160. Digitalcircuitry 158 enables interface module 157 to communicate with interfacecontroller module 154. Non-isolated analog circuitry 159 in interfacemodule 157 has coupled thereto a programming head 58 which, as would beappreciated by those of ordinary skill in the art, is used to establisha telemetry link between an implanted device and programmer 32. Inparticular, programming head 58 is placed over the implant site ofpacemaker 10 in a patient, and includes a telemetry coil fortransmitting and receiving RF signals.

As previously noted, pacemaker 10 provides digitized EGM signals up-linktelemetered to programmer 32. The telemetered EGM signals are receivedin programming head 58 and provided to non-isolated analog circuitry159. Non-isolated analog circuitry 159, in turn, converts the digitizedEGM signals to analog EGM signals (as with a digital-to-analogconverter, for example) and presents these signals on output linesdesignated in FIG. 9 as A EGM OUT and V EGM OUT. These output lines maythen be applied to a strip-chart recorder, CRT, or the like, for viewingby the physician. As these signals are ultimately derived form theintracardiac electrodes, they often provide different information thatmay not be available in conventional surface ECG signals derived fromskin electrodes. Pacemaker 10 may also be capable of generatingso-called marker codes indicative of different cardiac events that itdetects. A pacemaker with marker-channel capability is described, forexample, in U.S. Pat. No. 4,374,382 to Markowitz entitled "MarkerChannel Telemetry System for a Medical Device", which patent is herebyincorporated by reference herein in its entirety. The markers providedby pacemaker 10 may be received by programming head 58 and presented onthe MARKER CHANNEL output line from non-isolated analog circuitry 159.

Isolated analog circuitry 160 in interface module 157 is provided toreceive ECG and EP signals. In particular, analog circuitry 160 receivedECG signals from patient skin electrodes and processes these signalsbefore providing them to the remainder of the programmer system.Circuitry 160 further operates to receive electrophysiologic (EP)stimulation pulses from an external EP stimulator, for the purposes ofnon-invasive EP studies, as would be appreciated by those of ordinaryskill in the art. In order to ensure proper positioning of programminghead 161 over implanted device 10, circuitry is commonly provided forproviding feedback to the user that programming head 161 is insatisfactory communication with and is receiving sufficiently strong RFsignals from pacemaker 10. This feedback may be provided, for example,by means of a head position indicator, designated as 161 in FIG. 9. Headposition indicator 162 may be, for example, a light-emitting diode (LED)or the like that is lighted to indicate a stable telemetry channel.

Programmer 32 is also provided with a strip-chart printer or the like,designated in 163 in FIG. 9, which may be used, for example, to providea hard copy print-out of the A EGM or V EGM signals transmitted frompacemaker 10.

FIG. 10 illustrates the non-isolated circuitry 159 in more detail. TheRF signal is received through the programming head 161 which is heldwithin the uplink telemetry field of the implanted device. The RF signalcontains an FM encoded analog waveform. The encoding scheme is afrequency modulation that is proportional to analog voltage amplitudewith a base carrier frequency corresponding to 0.0 volts. This signal isinput to the demodulator block 170 where a digital signal representingthe analog input is demodulated from the RF transmission. The digitalsignal is converted to an analog waveform in the digital to analogconverter block 172. The analog signal is then fed to the measurementsystem 174. The measurement system measures the magnitude of the inputanalog waveform and generates a digital value that corresponds to themagnitude of the signal. The value is then held during the comparephase.

A look-up table 182 in the digital circuitry 158 contains calibrationvalues based on the model number of the implanted device. (This modelnumber is decoded from digital uplink telemetry previous to calibrationfunctions.) The calibration values from the table are loaded in thecompare block 180 simultaneously as the values from the measurementsystem. The values are compared and the output of the compare block is acontrol signal to the gain controller 178. The gain controller adjuststhe gain factor of the output driver 176 to correct the signal based onthe calibration function. The calibrated output driver signal is thenoutput to the chart recorder or screen display. FIGS. 8a and 8b showwhat the SQUARE₋₋ WAVE and DIFF₋₋ WAVE output signals, respectively looklike after having been transmitted by telemetry circuit 54 and printedon strip recorder 62.

As an alternative to transmitting the cardiac signals from leads 18-1,18-2, 18-3, and 18-4 to an external peripheral as described above withreference to FIG. 3, it has been further contemplated by the inventorsthat heart transplant monitoring may be accomplished by providing inpacemaker 10 circuitry for storing long-term averages of peak values ofthose signals. These stored values could be subsequently transmitted tothe external device for analysis. An implantable device capable ofcomputing long-term average values of various diagnostic values isextensively described in pending U.S. patent application Ser. No.07/881,996 filed on May 1, 1992 by Nichols et al., entitled "DiagnosticFunction Data Storage and Telemetry Out for Rate Responsive CardiacPacemaker", which application is hereby incorporated by reference in itsentirety.

The inventors have also contemplated a further refinement of thepresently disclosed embodiment of the invention, wherein an internalclock in pacemaker 10 would enable amplitude evaluation as describedhereinabove at periodic intervals, for example, every twenty-four hours.By performing the amplitude evaluation only at periodic intervals,advantages in memory and battery efficiency may be realized. Inaddition, this arrangement would provide a method of obtaining a stablebaseline of the values, since the effects of normal short-term orcycle-to-cycle variations in the cardiac signal would be minimized. Asan example, the amplitude evaluation could occur during the middle ofthe night to ensure the patient is at rest.

Still another refinement to the presently disclosed embodiment of theinvention has been contemplated, wherein an activity sensor is alsoprovided in pacemaker 10. As noted in the above-referenced Rosenbloomarticle, exercise-induced regional ischemia may also produce abrupt andsubstantial declines in the peak R-wave, which may be erroneouslyinterpreted as indicating rejection. If the present invention werepracticed with a pacemaker having an activity sensor, however,exercise-induced R-wave variations could be readily distinguished fromthe decline in peak R-wave amplitudes associated with rejection bysampling data during periods of patient inactivity.

Still another refinement to the presently disclosed embodiment of theinvention has been contemplated, wherein electrodes 18-1, 18-2, 18-3,and 18-4 of FIG. 2 are sequentially paced unipolarly with respect to thecan of pacemaker 10. The three non-paced electrodes monitor thewavefront propagation as the ventricles depolarize. Each sensing leadmonitors a different summation of conducted wavelets and, by monitoringthe signal arrival at each sensing site, cardiac conduction velocity andintrinsic cardiac tissue status may be monitored. This concept ofsensing twelve different sensing configurations allows for a morecomplete monitoring of cardiac tissue than the hereinabove-describedfour-site intrinsic waveform monitoring.

From the foregoing detailed description of a specific embodiment of theinvention, it should be apparent that a method and apparatus forcalibrating a telemetry channel has been disclosed. The disclosed methodand apparatus are particularly well-suited to the situation in which animplanted cardiac device is used to transmit electrical cardiac signalsto an external device, for the purpose of monitoring changes in peakamplitude of the cardiac signals. Such changes, as previously noted canbe indicative of certain cardiac conditions, such as rejection of atransplanted heart.

Although a particular embodiment of the present invention has beendisclosed herein in some detail, it is to be understood that this hasbeen done for the purposes of illustration only, and is not intended tolimit the scope of the present invention as defined in the appendedclaims. It is believed by the inventors that various alterations,modifications, and substitutions may be made to the disclosed embodimentof the invention without departing from the spirit and scope of theinvention. In particular, while in the disclosed embodiment a referencesignal having a known amplitude is transmitted on the telemetry channelin order to determine whether any attenuation of the reference signalamplitude has occurred in the telemetry channel, it is also contemplatedby the inventors that other types of reference signals, for instancesinusoidal signals or the like, may be provided in order to additionallyassess the telemetry channel's effect on the phase or frequency spectrumof the reference signal.

What is claimed is:
 1. A method of operating a telemetry system having atransmitter associated through physical proximity with a patient and areceiver, comprising the steps of:(a) generating a reference signalhaving at least one attribute having a defined value, in saidtransmitter; (b) acquiring an analog signal from a device that senses apatient attribute also associated through physical proximity with saidpatient for transmission by said transmitter; (c) transmitting saidreference signal and said analog signal from said transmitter to saidreceiver; (d) receiving said reference and analog signals transmitted instep (d); (e) measuring said attribute of said received referencesignal; and (f) calibrating said received analog signal as a function ofsaid measured attribute.
 2. A method in accordance with claim 1 whereinsaid step of generating a reference signal comprises generating a signalhaving a predetermined amplitude.
 3. A method in accordance with claim1, wherein said step of generating a reference signal comprisesgenerating a square wave having a predetermined amplitude.
 4. A methodin accordance with claim 1 wherein said step of generating a referencesignal comprises generating a sequence of alternating positive andnegative spikes having predetermined amplitudes.
 5. A method accordingto claim 1 or claim 2 or claim 3 or claim 4 wherein said calibratingstep comprises comparing said measured attribute with a known value ofsaid attribute and adjusting gain applied to said received analog signalas a function of the difference between said measured attribute and saidknown value.
 6. A method according to claim 1 or claim 2 or claim 3 orclaim 4 wherein said calibrating step comprises adjusting gain appliedto said received analog signal as a function of said measured attribute.7. A method according to claim 1 or claim 2 or claim 3 or claim 4wherein said calibrating step comprises comparing said measuredattribute with a known value of said attribute and correcting saidreceived analog signal as a function of the difference between saidmeasured attribute and said known value.